Abstract

Background

The post-genomic era of malaria research provided unprecedented insights into the
biology of Plasmodium parasites. Due to the large evolutionary distance to model eukaryotes, however, we
lack a profound understanding of many processes in Plasmodium biology. One example is the cell nucleus, which controls the parasite genome in a
development- and cell cycle-specific manner through mostly unknown mechanisms. To
study this important organelle in detail, we conducted an integrative analysis of
the P. falciparum nuclear proteome.

Results

We combined high accuracy mass spectrometry and bioinformatic approaches to present
for the first time an experimentally determined core nuclear proteome for P. falciparum. Besides a large number of factors implicated in known nuclear processes, one-third
of all detected proteins carry no functional annotation, including many phylum- or
genus-specific factors. Importantly, extensive experimental validation using 30 transgenic
cell lines confirmed the high specificity of this inventory, and revealed distinct
nuclear localization patterns of hitherto uncharacterized proteins. Further, our detailed
analysis identified novel protein domains potentially implicated in gene transcription
pathways, and sheds important new light on nuclear compartments and processes including
regulatory complexes, the nucleolus, nuclear pores, and nuclear import pathways.

Conclusion

Our study provides comprehensive new insight into the biology of the Plasmodium nucleus and will serve as an important platform for dissecting general and parasite-specific
nuclear processes in malaria parasites. Moreover, as the first nuclear proteome characterized
in any protist organism, it will provide an important resource for studying evolutionary
aspects of nuclear biology.